Acellular Gellan-gum based bilayered structures for the regeneration of osteochondral defects: a preclinical study

 In orthopaedics, the management and treatment of osteochondral (OC) defects remains an ongoing clinical challenge. Autologous osteochondral mosaicplasty has been used as a valid option for OC treatments although donor site morbidity remains a source of concern [1]. Engineering a whole structure capable of mimicking different tissues (cartilage and subchondral bone) in an integrated manner could be a possible approach to regenerate OC defects. In our group we have been proposing the use of bilayered structures to regenerate osteochondral defects [2,3]. The present study aims to investigate the pre-clinical performance of bilayered hydrogels and spongy-like hydrogels in in vivo  models (mice and rabbit, respectively), in both subcutaneous and orthotopic models. The bilayered structures were produced from Low Acyl Gellan Gum (LAGG) from Sigma-Aldrich, USA. Cartilage-like layers were obtained from a 2wt% LAGG solution. The bone-like layers were made of 2wt% LAGG with incorporation of hydroxyapatite at 20% and 30% (w/v). Hydrogels and spongy-like were subcutaneouly implanted in mice to evaluate the inflammatory response. Then, OC defects were induced in rabbit knee to create a critical size defect (4 mm diameter and 5 mm depth), and then hydrogels and sponges implanted. Both structures followed different processing methods. The hydrogels were injected allowing in situ  crosslinking. Unlike, the spongy-like were pre-formed by freeze-drying. The studies concerning subcutaneous implantation and critical size OC defect were performed for 2 and 4 weeks time, respectively. Cellular behavior and inflammatory responses were assessed by means of histology staining and biochemical function and matrix deposition by immunohistochemistry. Additionally, both OC structures stability and new cartilage and bone formation were evaluated by using vivo- computed tomography (Scanco 80). The results showed no acute inflammatory response for both approaches. New tissue formation and integration in the adjacent tissues were also observed, which present different characteristic behaviors when comparing hydrogels and sponges response. As future insights, a novel strategy for regeneration of OC defects can be designed encompassing both, hydrogels and spongy-like structures and cellular approaches. References: 1. Espregueira-Mendes J. et al. Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions. Knee Surgery, Sports Traumatology, Arthroscopy 20,1136, 2012. 2. Oliveira JM. et al, Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: Scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 27, 6123, 2006. 3. Pereira D R. et al. Gellan Gum-Based Hydrogel Bilayered Scaffolds for Osteochondral Tissue Engineering. Key Engineering Materials 587, 255, 2013.

An agent-based model to assess the attractiveness of industrial estates

This article describes the main approaches adopted in a study focused on planning industrial estates on a sub-regional scale. The study was supported by an agent-based model, using firms as agents to assess the attractiveness of industrial estates. The simulation was made by the NetLogo toolkit and the environment represents a geographical space. Three scenarios and four hypotheses were used in the simulation to test the impact of different policies on the attractiveness of industrial estates. Policies were distinguished by the level of municipal coordination at which they were implemented and by the type of intervention. In the model, the attractiveness of industrial estates was based on the level of facilities, amenities, accessibility and on the price of land in each industrial estate. Firms are able to move and relocate whenever they find an attractive estate. The relocating firms were selected by their size, location and distance to an industrial estate. Results show that a coordinated policy among municipalities is the most efficient policy to promote advanced-qualified estates. In these scenarios, it was observed that more industrial estates became attractive, more firms were relocated and more vacant lots were occupied. Furthermore, the results also indicate that the promotion of widespread industrial estates with poor-quality infrastructures and amenities is an inefficient policy to attract firms.

Development of advanced cell/tissue culture systems, based on enhanced polymeric scaffolds and sophisticated bioreactors, for tissue engineering applications

Programa Doutoral em Engenharia Biomédica

A bio-inspired computational model for motion detection

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Assessing the suitability of the minimum capture size and protection regimes in the gooseneck barnacle shellfishery

The suitability of a total-length-based, minimum capture-size and different protection regimes was investigated for the gooseneck barnacle Pollicipes pollicipes shellfishery in N Spain. For this analysis, individuals that were collected from 10 sites under different fishery protection regimes (permanently open, seasonally closed, and permanently closed) were used. First, we applied a non-parametric regression model to explore the relationship between the capitulum Rostro-Tergum (RT) size and the Total Length (TL). Important heteroskedastic disturbances were detected for this relationship, demon- strating a high variability of TL with respect to RT. This result substantiates the unsuitability of a TL-based minimum size by means of a mathematical model. Due to these disturbances, an alternative growth- based minimum capture size of 26.3 mm RT (23 mm RC) was estimated using the first derivative of a Kernel-based non-parametric regression model for the relationship between RT and dry weight. For this purpose, data from the permanently protected area were used to avoid bias due to the fishery. Second, the size-frequency distribution similarity was computed using a MDS analysis for the studied sites to evaluate the effectiveness of the protection regimes. The results of this analysis indicated a positive effect of the permanent protection, while the effect of the seasonal closure was not detected. This result needs to be interpreted with caution because the current harvesting based on a potentially unsuitable mini- mum capture size may dampen the efficacy of the seasonal protection regime.